Trafficking of ASIC1a channels between cellular compartments: role in neuroinflammation

OSVALDO D. UCHITEL; LIBIA CATALINA SALINAS; CARINA WEISSMANN

Cordoba

Simposio; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

SAN

Interleukin 6 (IL-6) is one of the main neuroinflammatory cytokines in the centralnervous system (CNS). CNS IL-6 is upregulated when neuroinflammationoccurs, determines changes in metabolic activity and can result in acidosis.Changes in regional pH levels in the brain have been observed in a numberof neurological and neurodegenerative disorders. ASIC (Acid sensing Ion)channels are sodium channels activated by tissue acidosis and thus becomeactive in many pathological conditions. ASIC1 is the most abundant ASIC subunitin the mammalian CNS, permeate sodium and slightly calcium ions and couldcontribute to intracellular calcium levels and neuronal injury in pathologicalconditions. We decided to analyze the role of IL-6 on ASIC1 channels. Weestablished a method to analyze the presence of the channel in the differentcellular compartments. Our preliminary results show that IL-6 determines theredistribution of ASIC1 channels to the plasma membrane of the cells and anincrease in calcium currents via ASIC1. Also, we studied dissociated mousehippocampal cultures. We incubated it with IL-6 and did inmunocytochemistryof the samples to detect ASIC1 and used calcium-sensitive dyes and ASIC1blockers to detect calcium currents posterior to ASIC activation. Theseresults point at a mechanism by which neuroinflammation could contribute toneurodegeneration and ASIC1 as a potential target in these conditions and amethod to analyze proteins in the different cell compartments.